Journal of Exercise & Organ Cross Talk

Abstract The aim of the present study was to investigate the effect of sprint interval training on Markers of bone metabolism and bone density in Male Wistar Rats under unhealthy high fat, sugar, salt Diet. The study design was an 8-week protocol consisting of three groups: Control (CO), Western diet (WD) and Western diet+Sprint interval training (SIT) (WD/SIT). WD rats received a high-fat, sugar, and salt diet, while WD/SIT rats followed the same diet combined with sprint interval training. The one-way ANOVA revealed significant differences between groups for all variables (p<0.05). Effect sizes (η²) ranged from 0.47 to 0.99, indicating large effects for bone density (η²=0.99), ALP(η²=0.77), phosphorus (η²=0.74), and calcium (η²=0.47).  Post-hoc analysis by LSD test showed that the WD group exhibited a significantly lower femur bone density percentage (24.09±2.32) compared to both the control (58.40±1.64) and WD/SIT (47.67±1.60) groups (p<0.001). Regarding bone metabolism markers, the WD/SIT group demonstrated significantly reduced serum ALP levels (195.67±20.83IU/L) compared to the control (248.33±29.30IU/L) and WD (253.17±38.46IU/L) groups (p<0.001). For serum phosphorus, the WD/SIT group (5.68±0.58 mg/dL) was significantly lower than the control (7.68±0.63 mg/dL) and WD (8.58±0.78mg/dL) groups (p<0.001). Furthermore, serum calcium levels in the control group (10.27±0.80 mg/dL) were significantly higher than in the WD/SIT (8.92±0.61 mg/dL) and WD (9.18 ± 0.28 mg/dL) groups (p< 0.01). These results indicate that a high-calorie, high-salt diet had a negative effect on bone metabolism. However, sprint interval training partially attenuated these adverse effects.

Abstract This study aimed to investigate the effects of high-intensity interval training (HIIT) on Adiponectin receptor 1 (AdipR1) gene expression in breast tumor tissue and serum levels of glutathione peroxidase (GPX) and glutathione reductase (GR) in a murine model of breast cancer. Sixteen male BALB/c mice were inoculated subcutaneously with 4T1 murine mammary carcinoma cells (5 × 10⁵ cells/mouse). One week post-inoculation, mice were randomly assigned to either a tumor-bearing control group (Tumor, n=8) or a tumor-bearing group subjected to HIIT (Tumor+HIIT, n=8). The HIIT protocol was performed on a motor-driven treadmill five days/week for four weeks, consisting of six 2-minute high-intensity intervals (18–25 m/min, 80–90% VO₂max) interspersed with 3-minute active recovery periods (5–9 m/min). Twenty-four hours after the final session, tumor tissues were excised for AdipR1 gene expression analysis via quantitative real-time PCR (2^-ΔΔCT method), and serum samples were collected for assessment of GPX and GR levels using ELISA. Statistical comparisons were performed using independent samples t-tests (p<0.05). HIIT significantly upregulated AdipR1 gene expression in breast tumor tissue compared to the control group (p<0.0001). Serum GPX levels were significantly decreased in the Tumor+HIIT group compared to the Tumor control group (p<0.0001). However, no significant difference was observed in serum GR levels between the two groups (p=0.7499). These findings suggest that HIIT may influence breast cancer progression through adiponectin-mediated pathways and oxidative stress regulation, providing a potential non-pharmacological adjunctive strategy for breast cancer management. Further studies are warranted to elucidate the underlying molecular mechanisms and clinical implications.

Abstract Hepatic gene expression of inflammatory and growth factors such as IL-8 and bFGF2 may be modulated in melanoma metastasis. Non-pharmacological interventions like exercise and anti-inflammatory supplements represent potential complementary strategies for modification. This study aimed to investigate the effects of aerobic exercise, pineapple extract supplementation, and their combination on the hepatic expression of CXCL2/IL-8 HOMOLOG and bFGF2 genes in a murine melanoma model. Melanoma-bearing mice were allocated into four groups (n=5 per group): Control, Aerobic Exercise, Pineapple Extract Supplement, and Aerobic Exercise + Pineapple Extract. After the intervention period, liver tissue was analyzed for CXCL2/IL-8 HOMOLOG and bFGF2 gene expression via one-way ANOVA and Tukey HSD test. Pearson correlation assessed the relationship between the two genes. A significant difference was observed in CXCL2/IL-8 HOMOLOG gene expression between groups (F=4.211, p=0.0239). Post hoc analysis revealed that only the combined Aerobic Exercise + Pineapple Extract group showed a significant decrease in hepatic CXCL2/IL-8 HOMOLOG compared to the Cancer Control group (p=0.0251). In contrast, no significant difference was found in bFGF2 gene expression across groups (F=1.425, p=0.2745). Correlation analysis indicated a significant negative relationship between CXCL2/IL-8 HOMOLOG and bFGF2 exclusively in the Cancer Control group (r = -0.948, p=0.013). The combination of aerobic exercise and pineapple extract supplementation significantly reduces hepatic CXCL2/IL-8 HOMOLOG expression in melanoma-bearing mice, suggesting a potential synergistic effect in modulating the hepatic inflammatory microenvironment. The distinct lack of effect on bFGF2 and the specific negative correlation in controls highlight pathway-selective responses.

Abstract This randomized controlled trial evaluated the effects of combined mobile-based digital education ("DiabetiFit Pro") and aerobic-resistance exercise on treatment adherence, glycemic control, and tissue markers (lipotoxicity, sarcopenia, and necrosis) among underserved type 2 diabetes patients. In this 12-week RCT, 250 patients (mean age 54.3±10.7 years; HbA1c 9.2%) from underserved Iranian regions were randomized to intervention (n=125; 3 weekly sessions: 10-min app-based education + 35-50 min ACSM-guided exercise) or control (n=125; usual care). Primary outcomes were HbA1c and MMAS-8 adherence scores. Secondary outcomes included glycemic variability and tissue biomarkers. Analysis used ITT with ANCOVA, regression, and χ² (α=0.05). Intervention produced superior HbA1c reduction (-1.70% vs -0.70% control; between-group diff: -1.00%, η²=0.18, p<.001) and adherence gains (+1.30 vs +0.40 points; η²=0.16, p<.001). High adherence increased from 23.2% to 48.8% (χ²=22.45, p<.001). Dose-response: modules completed explained 11.5% HbA1c variance (β=-0.34); app hours predicted 16.8% adherence variance (β=0.41). Favorable lipotoxicity/ sarcopenia improvements observed. Combined digital education-exercise interventions significantly enhance adherence, glycemic control, and tissue health in underserved T2DM populations, demonstrating dose-response efficacy and clinical meaningfulness per ADA standards. Health systems should scale such integrated mHealth platforms.

Abstract This study investigated the effects of high intensity interval training (HIIT), nano-selenium supplementation, and their combination on the expression of LDHA, LDHB, and the LDHA/LDHB ratio in mice breast tumor tissue. Female mice (n = 32) were inoculated with mammary adenocarcinoma cells and randomly assigned to four groups (n = 8 each): tumor control (Tu), tumor + HIIT (Tu + Ex), tumor + nano-selenium (Tu + Nsel, 0.5 mg/kg/day orally), and tumor + HIIT + nano-selenium (Tu + Ex + Nsel). HIIT was performed on a treadmill (30 min/day, 5 days/week) for four weeks. One way ANOVA revealed significant differences among groups for LDHA expression (F = 38.66, p < 0.0001). Compared to the Tu group, all intervention groups (Tu + Ex, Tu + Nsel, and Tu + Ex + Nsel) showed a significant increase in LDHA expression (p < 0.05). The greatest increase was observed in the combined treatment group (Tu + Ex + Nsel), which was significantly higher than both Tu + Ex and Tu + Nsel (p < 0.001). For the LDHA/LDHB ratio, a significant overall effect was found (F = 163.87, p < 0.0001). The Tu + Nsel group exhibited a significant increase in the ratio compared to the Tu group (p < 0.05), whereas both Tu + Ex and Tu + Ex + Nsel showed a significant decrease in the ratio (p < 0.05). The ratio in the Tu + Nsel group was also significantly higher than in the two exercise containing groups (p < 0.05). HIIT and nano-selenium independently upregulate LDHA expression in breast tumor tissue, with an additive effect when combined. However, only nano-selenium alone increased the LDHA/LDHB ratio, while exercise based interventions (with or without nano-selenium) decreased this ratio. These findings suggest that exercise and nano-selenium differentially shift the balance between LDHA and LDHB, potentially influencing tumor lactate metabolism and the tumor microenvironment.

Abstract To investigate the individual and combined effects of six weeks of aerobic exercise and hydroalcoholic extract of Urtica dioica (nettle) on tumor volume, body weight, and interleukin-10 (IL-10) levels in both serum and tumor tissue in male C57BL/6 mice bearing B16F10 melanoma tumors. Thirty-two male C57BL/6 mice (6–8 weeks old, 12–14 g) were randomly assigned to four equal groups (n=8): Control, Aerobic Exercise (AE), Nettle Extract (NE), and Combined (AE+NE). Melanoma was induced via surgical implantation of B16F10 tumor fragments. The AE protocol consisted of treadmill running for 6 weeks (5 days/week, progressing from 20 to 30 minutes/session at 6–16 m/min). The NE group received intraperitoneal injections of hydroalcoholic nettle extract (200 mg/kg body weight). The combined group received both interventions. The combined AE+NE group showing a significant reduction in tumor volume compared to the control group (p = 0.0186). One-way ANOVA revealed significant differences in serum IL-10 across groups (F=9.811, p=0.0001), with significant increases observed in the AE (p=0.0003) and AE+NE (p = 0.0005) groups compared to controls. For tumor IL-10, a significant difference was also found across groups (F = 3.047, p = 0.0451), with the combined AE+NE group showing a significant decrease (p = 0.0435) compared to the control group. No significant correlation was found between serum and tumor IL-10 levels in any group (p>0.05). The combined intervention significantly suppressed tumor growth compared to controls and was associated with increased serum IL-10 levels but decreased IL-10 levels within the tumor microenvironment, suggesting a complex, compartment-specific immunomodulatory effect.

Abstract Physical inactivity is a major global determinant of non-communicable diseases, particularly in industrial and occupational environments where structural and environmental barriers limit regular engagement in physical activity. Although the health benefits of aerobic exercise are well established, less attention has been given to the physiological specificity of exercise intensity and its translation into feasible health promotion strategies in real world settings. Current evidence indicates that moderate intensity running (approximately 50–70% heart rate reserve, 46–63% VO₂max, or Borg RPE 12–14) induces coordinated multisystem signaling responses that support metabolic regulation and inflammatory balance. These responses include favorable modulation of myokines, adipokines, neurotrophic factors, and immunoregulatory mediators involved in metabolic homeostasis. Particular attention is given to the context dependent role of interleukin 6, highlighting the distinction between its transient exercises induced signaling effects and the chronic elevations associated with metabolic and inflammatory diseases. In addition to mechanistic insights, this review discusses translational considerations such as adherence, safety, and long term sustainability of moderate intensity running programs in occupational populations. The HamGhadam (Step for Good) initiative implemented by Gol Gohar Mining and Industrial Company is presented as a descriptive workplace case example illustrating how structured physical activity programs can be incorporated into corporate wellness initiatives. The manuscript does not claim empirical validation of the program’s effectiveness but highlights its potential as a practical model for workplace health promotion. Overall, smart running is framed as a biologically efficient and potentially scalable strategy that conceptually bridges molecular exercise biology with population level physical activity promotion.

Abstract Dear Editor-in-Chief As our field continues to map the intricate networks of exercise-induced organ crosstalk, the concept of "intelligent substrate utilization" remains a compelling yet incompletely understood frontier. While much focus has been placed on the acute actions of individual myokines and exerkines, a more integrated, systems-level perspective is emerging‒one that positions chronic exercise adaptation as the remodeling of an endocrine matrix. This matrix, I propose, governs a form of metabolic intelligence characterized by the dynamic, context-dependent allocation and utilization of energetic substrates across organs. Recent breakthroughs are beginning to decode the spatiotemporal logic of this system, moving beyond simple linear pathways to reveal complex networks that enable the body to adapt fuel metabolism with remarkable precision. Three key advances, in particular, illuminate new variables and pathways that underpin this intelligent substrate utilization. First, the "Myokine-mediated Multi-organ Metabolic Network" theory provides a comprehensive framework for understanding how myokines act not in isolation but as a coordinated signaling hub. This work meticulously maps interactions from skeletal muscle to over a dozen organs, orchestrating programs across six biological axes, including energy substrate flux. Crucially, the framework highlights how myokines function as pleiotropic modulators within an integrated system, a property that fundamentally reshapes our view of substrate allocation. It suggests that the "intelligence" of the system lies not in any single molecule but in the emergent properties of this multi-target network (Chen et al., 2025). Second, a landmark systems genetics study, leveraging multi-tissue data from the MoTrPAC consortium, reveals that endurance training fundamentally remodels the entire inter-organ endocrine network. This work demonstrates that the strength and specificity of endocrine signals between tissues are significantly altered with training. Notably, subcutaneous white adipose tissue (scWAT) emerged as a major endocrine hub, and extracellular matrix factors, along with secretory WNT signaling molecules, were identified as central mediators of training adaptations. These discoveries offer a crucial new variable‒the network-wide remodeling of endocrine crosstalk‒demonstrating that "intelligent" substrate use is a learned property of the whole system, not a pre-programmed one. The bidirectional and training-dependent plasticity of tissue-pair signaling adds a new layer of complexity to how we model metabolic control during exercise (Ahn et al., 2025). Finally, the identification of novel metabolic signaling molecules, termed "metabokines" and "lipokines," expands the classic myokine paradigm to include bioactive metabolites and lipids as direct mediators of inter-organ signaling. These molecules are not mere energy sources but are sophisticated signals that coordinate systemic adaptations. This reframes substrate utilization itself as a mode of communication: the very act of metabolizing a substrate can generate a signal that informs and directs systemic metabolic priorities (Gad et al., 2024). These three insights‒the multi-organ myokine network, the training-induced remodeling of the endocrine matrix, and the signaling roles of metabolites‒converge to describe a system with genuine adaptive intelligence. Chronic exercise, through this lens, is not simply a stressor but an educational process for the body's metabolic network, teaching it to anticipate demands and allocate resources with greater efficiency and precision. I write this letter to the Journal of Exercise and Organ Crosstalk because it stands at the ideal intersection to champion such a systems-level, integrative approach. Pursuing these ideas will require not only advanced multi-omics but also sophisticated computational modeling to predict network-level adaptive strategies. This is the central challenge for our field: to decode the syntax of exercise-induced communication.

Abstract This study aimed to investigate the effects of eight weeks of resistance training (Ex), vitamin D supplementation (VD), and their combination (VD+Ex) on insulin resistance (HOMA IR), glycemic control (HbA1c, fasting glucose), inflammatory markers (interleukin 6 [IL 6] and C reactive protein [CRP]), and anthropometric measures in men with T2DM. In this single blind randomized controlled trial, 40 men with T2DM (aged 40–55 years) were randomly allocated into four groups (n=10 each): placebo control (PI), vitamin D supplementation (2000 IU/day, VD), resistance training (three sessions/week, 60–70% of 1RM, progressive overload, Ex), and combined VD+Ex. All participants maintained their usual diet, lifestyle, and anti diabetic medications. Fasting blood samples were collected pre and post intervention to measure serum glucose, insulin, 25 hydroxy vitamin D, IL 6, and CRP. HOMA IR was calculated. Post hoc analysis showed that the Ex group had significantly lower HOMA IR than the placebo group (p=0.002), and the VD+Ex group had significantly lower HOMA IR compared to both placebo (p<0.001) and VD alone (p=0.001). The comparison between VD+Ex and Ex was not statistically significant (p>0.05). No significant difference in HbA1c was observed (p=0.210). For body fat percentage, both Ex (p=0.043) and VD+Ex (p<0.001 vs. placebo;p=0.009 vs. VD) showed significant reductions. IL 6 levels were significantly lower in the Ex and VD+Ex groups compared to placebo and VD groups (p<0.001 for both). No significant changes were found in CRP levels (p=0.078).

Abstract This semi-experimental study employed a pre-test–post-test design with a control group to investigate the effects of an eight-week sport metric training program on selected hematological indices and physical performance variables in adolescent male soccer players. Thirty participants (aged 13–16 years) were randomly assigned to either an experimental group (n = 15) or a control group (n = 15). The experimental group performed sport metric training three sessions per week for eight weeks, in addition to their routine soccer training. The control group continued only their standard soccer sessions. Hematological indices (hemoglobin, hematocrit, and blood viscosity) were measured from venous blood samples, while physical performance was assessed using the 36-meter sprint test (for speed) and the Illinois agility test. Following the intervention, the experimental group showed significant improvements compared to the control group. Hemoglobin and hematocrit levels increased meaningfully (P ≤ 0.05), suggesting enhanced oxygen-carrying capacity of the blood. Blood viscosity decreased significantly (P ≤ 0.05), which may indicate improved blood flow and reduced circulatory resistance. In terms of physical performance, the experimental group exhibited substantial reductions in sprint time (36-meter sprint) and agility time (Illinois test), both reaching statistical significance (P ≤ 0.05) with large effect sizes. In conclusion, eight weeks of sport metric training produced favorable changes in hematological profiles and marked enhancements in speed and agility performance among adolescent male soccer players. The findings suggest that targeted, sport-specific training programs can serve as a valuable supplement to routine soccer training during adolescence, supporting both physiological development and on-field performance.

Abstract This study investigated the effects of high-intensity interval training (HIIT) and a multi-strain probiotic mixture, on the intestinal expression of FXR and PPAR-γ in a rat model of type 2 diabetes mellitus (T2DM). Forty male Wistar rats were randomly assigned to five groups (n=8): Healthy Control (HC), Diabetic Control (DC), Diabetic+HIIT (DH), Diabetic+Probiotic (DP), and Diabetic+HIIT+Probiotic (DHP). T2DM was induced via a single intraperitoneal injection of nicotinamide (95 mg/kg) followed by streptozotocin (STZ, 55 mg/kg). The HIIT protocol was performed on a rodent treadmill for 8 weeks (5 sessions/week). The probiotic mixture (Lactobacillus rhamnosus GG, Lactobacillus casei, Lactobacillus reuteri; 1×10¹⁰ CFU/mL each) was administered daily via oral gavage. Diabetes induction significantly downregulated the intestinal expression of both FXR and PPAR-γ compared to healthy controls (p<0.001). HIIT and probiotic interventions, individually, significantly increased the expression of both nuclear receptors compared to the diabetic control group (p<0.001). Notably, the combined HIIT and probiotic intervention (DHP) produced the highest expression levels of FXR and PPAR-γ, which were significantly greater than either intervention alone (p<0.01) and restored FXR expression to levels comparable to healthy controls. Both HIIT and multi-strain probiotic supplementation effectively upregulate the intestinal expression of FXR and PPAR-γ in diabetic rats, with the combination exerting a synergistic effect. These findings identify a novel mechanism by which lifestyle interventions may restore intestinal metabolic function and inter-organ communication in T2DM, highlighting the therapeutic potential of targeting the gut through combined exercise and probiotic strategies.

Abstract This study was designed to conduct a bibliometric analysis of Iranian research on the effects of various resistance training protocols on muscle hypertrophy. The analysis examined temporal publication trends, prolific authors, leading research institutions, and prominent journals in this field. All relevant articles published up to the year 1403 (2024) were retrieved from the MagIran database. Inclusion criteria were limited to original peer-reviewed research articles published in Persian, while conference abstracts and other non-journal sources were excluded. Data were analyzed using VOSviewer software to perform co-authorship and keyword co-occurrence analyses. Between 1390 and 1403 (2011–2024), a total of 31 articles were published in this domain. Most publications were authored by faculty members of public (state) universities. Approximately 65% of the articles appeared in journals affiliated with the Ministry of Science, Research and Technology, whereas 35% were published in medical sciences journals. Keyword analysis indicated that “resistance training” and “muscle hypertrophy” were the most frequent and central terms, with clustering results demonstrating strong interconnections among core research topics. Overall, the findings of this bibliometric analysis provide a structured overview of the research landscape and offer a roadmap for identifying research gaps, publication patterns, and future research priorities in the Iranian context.

Abstract Melanoma is an aggressive malignancy with a high propensity for metastasis, particularly to the liver. This study investigated the individual and combined effects of resistance training (RT) and pineapple extract (PE) supplementation on primary melanoma tumor growth and the expression of hepatic apoptotic markers (Bax, Bcl-2) in a murine model. C57BL/6 mice bearing subcutaneous B16F10 melanoma tumors were allocated to four groups: Tumor Control (TC), RT, PE, and Combined (RT+PE). The six-week intervention consisted of ladder-climbing RT and/or oral PE supplementation. Tumor volume was measured throughout the study. Upon completion, hepatic Bax and Bcl-2 gene expression was analyzed via qPCR. While RT and PE alone did not significantly affect tumor volume, the Combined (RT+PE) group showed a significant reduction compared to the TC group (p<0.05). In the liver, all intervention groups (RT, PE, and Combined) significantly decreased pro-apoptotic Bax expression and increased anti-apoptotic Bcl-2 expression relative to the TC group (p<0.05). The combination of resistance training and pineapple extract exhibits a synergistic effect in reducing primary melanoma tumor growth. Furthermore, both interventions independently and collectively modulate systemic apoptotic markers in the liver, suggesting a potential role in influencing the hepatic microenvironment. This non-invasive combinatorial approach may represent a promising complementary strategy for managing melanoma progression and its systemic effects.

Abstract Sciatic nerve injury results in significant functional impairment and is associated with neuroinflammatory responses. While lithium and exercise have shown independent neuroprotective potential, their combined effects remain less explored. This study investigated the therapeutic efficacy of lithium, resistance training, and their combination on functional recovery and neuroinflammatory markers in a rat model of sciatic nerve injury. Twenty-five rats were randomly divided into five groups: Sham, Model (sciatic nerve injury), Model+Lithium, Model+Resistance training, and Model+Lithium+Resistance training. Lithium carbonate (10 mg/kg, i.p.) was administered for 5 days, and resistance training was conducted for 6 weeks, with both interventions starting 24 hours’ post-injury. Functional recovery was assessed using the beam walk test. Neuroinflammation was evaluated by measuring the activity of myeloperoxidase (MPO) and nitric oxide (NO) in the cerebrospinal fluid at the end of the 6-week intervention period. Sciatic nerve injury (Model group) induced a significant deficit in beam test performance compared to the Sham group (p < 0.001). All treatment groups (Lithium, Resistance training, and Combined) showed significant improvement in functional scores compared to the Model group, with the Combined treatment group showing significantly greater recovery than either monotherapy (p < 0.05). Furthermore, the Model group exhibited a significant increase in MPO and NO levels. Resistance training alone and in combination with lithium significantly attenuated this increase (p < 0.0001). Interestingly, lithium monotherapy did not reduce the elevated neuroinflammatory markers. Our findings demonstrate that resistance training alone effectively reduces neuroinflammation and improves functional recovery after sciatic nerve injury. The combination of lithium and resistance training yields a synergistic effect, resulting in the most significant functional improvement, suggesting a promising combined therapeutic strategy for peripheral nerve injury.

Abstract The integration of herbal supplementation with exercise training may offer a novel hybrid strategy that bridges traditional medicine and modern performance science to enhance recovery and physical outcomes. This study aimed to evaluate the synergistic effects of cinnamon supplementation and Tabata-style high-intensity interval training (HIIT) on metabolic and performance outcomes in young male military cadets. Forty-eight healthy cadets were randomly assigned to four groups: Tabata training (T), cinnamon supplementation (S), Tabata + cinnamon (TS), and control (C). The intervention lasted six weeks, consisting of thrice-weekly Tabata sessions (87–100% HRmax) and daily oral cinnamon supplementation (1.5 g/day). Assessments conducted before and after the intervention included body composition, VO₂max, post-exercise blood lactate levels, and combat readiness scores based on the Army Combat Fitness Test. Statistical analysis employed paired t-tests and ANCOVA at a significance level of p < 0.05. Significant improvements were observed in the TS group compared to control: VO2max increased (p = 0.001), post-exercise lactate decreased (−1.93 mmol/L, p = 0.001), and combat readiness scores improved substantially (+63.6 points, p = 0.001). Comparable but less pronounced improvements were observed in the Tabata-only and cinnamon-only groups. No adverse effects were reported. The findings suggest that cinnamon—a time-honored medicinal spice—may potentiate the effects of high-intensity training by improving aerobic capacity, lactate clearance, and combat readiness. This study provides translational evidence supporting cinnamon as a safe, natural, and affordable traditional functional food that can enhance physical performance and metabolic resilience in tactical populations. The integration of traditional herbal supplementation with modern training paradigms offers a promising avenue in the evolving field of evidence-based traditional medicine.

Abstract Aerobic exercise has been proposed as a non-pharmacological intervention to modulate inflammatory gene expression, yet the molecular mechanisms remain incompletely understood. This study investigated the effects of a 12-week moderate-intensity aerobic exercise intervention on the mRNA expression levels of inflammation-related genes (TNF-α, IL-6, and IL-10) in peripheral blood mononuclear cells (PBMCs) of overweight individuals. Forty-five overweight adults (BMI 25-29.9 kg/m²) were randomly assigned to either an aerobic exercise group (n=30) or a sedentary control group (n=15). The exercise protocol consisted of supervised moderate-intensity aerobic training (60-75% HRmax) for 45-60 minutes, 5 days per week for 12 weeks. Blood samples were collected pre- and post- intervention for gene expression analysis using quantitative real-time PCR and protein quantification via ELISA. Following the 12-week intervention, the exercise group demonstrated significant reductions in TNF-α mRNA expression (−52.3%, p<0.001) and IL-6 expression (−47.8%, p<0.001) compared to baseline. Conversely, IL-10 expression increased significantly (+68.4%, p<0.001). Plasma protein concentrations paralleled these changes, with TNF-α decreasing from 8.6±2.1 to 4.9±1.3 pg/mL (p<0.001), IL-6 from 5.8±1.7 to 3.2±0.9 pg/mL (p<0.001), and IL-10 increasing from 3.1±0.8 to 5.6±1.2 pg/mL (p<0.001). Body mass index decreased significantly in the exercise group (−2.3 kg/m², p<0.001) with concurrent improvements in cardiorespiratory fitness (VO₂max increased by 18.7%, p<0.001). Moderate-intensity aerobic exercise effectively modulates the inflammatory gene expression profile in overweight individuals by downregulating pro-inflammatory genes (TNF-α and IL-6) and upregulating the anti- inflammatory gene (IL-10). These molecular adaptations may contribute to reduced inflammation and improved metabolic health in this population.

Abstract Rapid industrial expansion in Sirjan has reshaped occupational routines in ways that constrain daily movement and heighten metabolic vulnerability. While the health benefits of physical activity are well established, this narrative review advances the argument that the more fundamental deficit in such environments is the erosion of movement literacy—the cognitive, physiological, and behavioral capacity to understand, interpret, and intentionally engage in health sustaining physical activity. Drawing on evidence from exercise physiology, metabolic science, and occupational health, we conceptualize movement literacy as a multidimensional construct comprising awareness of exercise induced mechanisms, interpretation of bodily cues, and the ability to apply this knowledge to everyday behavior. Using the Gol Gohar industrial community as an illustrative case, we describe how limited literacy in these domains contributes to sedentary patterns among workers and outline how the Gol Gohar Sports Club operationalizes a literacy oriented model through targeted public education initiatives, coach led instructional programs, and awareness based practices such as “smart running.” By synthesizing mechanistic pathways—including glucose regulation, inflammatory modulation, neuroendocrine adaptation, and myokine signaling—the review positions movement literacy as a missing but necessary dimension in industrial health policy. We argue that enhancing this form of literacy may serve as a scalable strategy to mitigate metabolic risk and integrate exercise knowledge into routine occupational life.

Abstract Irisin, a myokine cleaved from the membrane protein Fibronectin type III domain-containing protein 5 (FNDC5), has emerged as a critical exercise-induced hormone. It is implicated in the browning of white adipose tissue, enhanced metabolic rate, and potential anabolic processes. In bodybuilding, where precise manipulation of training variables—specifically repetitions (reps) and sets—is paramount, understanding how these variables influence irisin secretion could optimize both physique and health outcomes. This narrative review aims to synthesize current evidence on the effects of resistance training protocols, with a focus on reps and sets, on irisin secretion. Furthermore, it explores the potential subsequent benefits of elevated irisin levels for bodybuilders, including its putative roles in fat metabolism, muscle remodeling, and overall metabolic health. Evidence suggests that high-volume resistance training protocols, characterized by multiple sets (≥3) and moderate repetitions (8-12 reps), may be potent stimulators of irisin release. This secretion is hypothesized to be mediated by muscle contraction-induced PGC-1α expression. Elevated irisin levels are often correlated with improved lipid oxidation, which could aid in cutting phases by promoting a leaner physique. Additionally, preclinical and some human studies suggest irisin may support muscle hypertrophy through enhanced nutrient partitioning and autocrine/paracrine signaling, though this mechanism requires further elucidation. Strategic manipulation of resistance training volume and intensity may represent a viable method for modulating irisin secretion. Incorporating protocols that could elevate this myokine might provide bodybuilders with a dual advantage: enhancing metabolic efficiency to reduce adipose tissue and potentially supporting muscle growth and recovery. However, the current evidence is not yet definitive, and more research is needed to confirm these links.

Abstract This study investigated the effects of resistance training and pineapple extract consumption on intratumoral NF-κB and LIN28B gene expression and serum TNF-α levels in a murine C57 melanoma model. Twenty C57BL/6 mice were allocated into four groups (n=5/group): melanoma tumor control (MT), MT with resistance training (MT+RT), MT with pineapple extract (MT+PJ), and MT with combined intervention (MT+RT+PJ). The RT protocol and PJ administration (300 mg/kg/day via gavage) were conducted for six weeks’ post-tumor induction. Serum TNF-α was quantified by ELISA, and tumor gene expression of NF-κB and LIN28B was analyzed via RT-PCR. Data were analyzed using one-way ANOVA followed by Tukey's post hoc test. All three intervention groups exhibited a significant downregulation of NF-κB and LIN28B gene expression in tumor tissue compared to the MT control group (p<0.05). Conversely, serum TNF-α levels were significantly elevated in the intervention groups relative to the control (p<0.05). Resistance training and pineapple extract consumption, both individually and in combination, significantly modulated pro-tumorigenic pathways by suppressing intratumoral NF-κB and LIN28B expression, despite an observed increase in systemic TNF-α.

Abstract This study aimed to evaluate the individual and combined effects of aerobic training (AT) and pineapple supplementation (extract) on programmed cell death protein 1 (PD-1) gene expression within the tumor microenvironment and on systemic interleukin-10 (IL-10) levels in a murine melanoma model. Twenty C57BL/6 mice were randomly assigned into four groups (n=5 per group) following melanoma tumor induction: Tumor control, AT, Pineapple Supplement (PS), and AT+PS. The AT group underwent a structured aerobic training program, while the PS group received pineapple extract (300 mg/kg/day) via oral gavage for six weeks. Serum IL-10 concentrations were quantified by ELISA, and PD-1 mRNA expression in tumor tissue was analyzed using quantitative RT-PCR. All intervention groups—AT, PS, and their combination—resulted in a significant downregulation of PD-1 gene expression within the tumor compared to the control group (p < 0.05). In contrast, neither AT nor PS alone significantly altered systemic IL-10 levels. The combination therapy (AT+PS) produced the most pronounced suppression of PD-1 and was the only intervention to elicit a significant, though modest, reduction in serum IL-10. These findings indicate that the primary immunomodulatory effect of these interventions is localized to the tumor microenvironment and is largely independent of systemic IL-10 signaling. The synergistic combination of aerobic training and pineapple supplementation potently suppresses PD-1 gene expression, suggesting a promising, non-pharmacological strategy for enhancing anti-tumor immunity. Further investigation is required to confirm these effects at the protein level and to elucidate the underlying mechanisms.

Abstract The pursuit of peak athletic performance is increasingly driven by technological innovation. This narrative review explores the role of emerging technologies in monitoring, analyzing, and enhancing the capabilities of athletes. We focus on the crosstalk between specific organ systems-the brain, the musculoskeletal system, and the cardiovascular system-and the technologies designed to interface with them. Key areas discussed include neurotechnology for cognitive training and recovery, wearable sensors and imaging for musculoskeletal assessment, and advanced biomonitoring for cardiovascular and metabolic optimization. A summary table synthesizes the technologies, their target organs, and primary applications. While these tools offer unprecedented insights, we also discuss challenges related to data interpretation, integration, and accessibility. The future of athletic performance lies in a holistic, technology-enabled understanding of the athlete as a complete, interconnected system.

Abstract Dear Editor-in-Chief
We are pleased to submit our manuscript, "Unveiling Systemic Complexity: The Role of Artificial Intelligence in Integrative Athlete Monitoring," for peer review and potential publication as a Letter in Exercise & Organ Crosstalk. 
The current paradigm in athlete monitoring, while rich in data from wearables and physiological assays, often struggles with a fundamental challenge: synthesizing disparate data streams into a coherent, holistic model of the athlete's state. While systematic reviews highlight the potential of AI for multivariate injury risk assessment (Claudino et al., 2019), and recent studies demonstrate success in forecasting complex, temporal phenomena like sleep and performance (Mateus et al., 2024), a generalized AI framework for modeling the underlying cross-talk between physiological systems is still lacking. Traditional statistical methods, and even many current AI applications, remain inadequate for fully capturing the non-linear, dynamic, and highly individualized nature of inter-organ communication and systemic response to exercise stress.
Our manuscript directly addresses this challenge by proposing a novel framework that leverages the power of artificial intelligence (AI) and machine learning (ML). We argue that techniques such as recurrent neural networks (RNNs) and graph neural networks (GNNs) are uniquely suited to model the very "cross-talk" that is the focus of your journal. These models can integrate data from the cardiovascular, musculoskeletal, endocrine, and nervous systems to identify complex, latent patterns that predict performance outcomes, fatigue, and injury risk far more accurately than univariate or linear multivariate models.
This work aligns perfectly with the scope of Exercise & Organ Cross Talk, as it moves beyond viewing physiological systems in isolation.We provide a perspective on how AI can act as the essential computational tool to finally quantify and model the deep, systemic interactions that define an athlete's adaptation to training. We believe this perspective will be of significant interest to your readership, stimulating new research at the intersection of computational biology, exercise physiology, and sports medicine.

Abstract The aim of this study was to investigate the effects of an exercise program (EP) in combination with functional electrical stimulation (FES) on bone mass density (BMD) and bone turnover markers (BTMs) in osteopenic postmenopausal women. In this semi-experimental study, 45 women aged 61.25 ± 4.1 years who were classified as osteopenic (-2.5 < T-score < -1) were divided into three groups: 1) EP + FES, 2) EP and 3) control. The EP + FES and EP groups participated in a combined aerobic (45-60% HRR) and strength program for 90 minutes three times a week for 12 weeks. In the EP + FES group, FES with a frequency of 45 Hz and a pulse width of 300 microseconds was applied to the lumbar and hip area. Blood samples were taken at the beginning of the study and again after 12 weeks to determine BMDs. BMD was measured using dual-energy X-ray absorptiometry (DXA). After 12 weeks, cross-linked type 1 collagen C-telopeptide (sCTX) (p=0.002) and pyridinoline (PYD) (p=0.001) levels decreased significantly, while vitamin D (p=0.002), PINP/PYD ratio (p=0,032), the ALP/PYD ratio (p=0.004) and the ALP/CTX-1 ratio (p=0.010) increased significantly in both the EP+FES and EP groups compared to the control group. The EP+FES group showed a significant increase in lumbar (p=0.048) and hip BMD (p=0.038) compared to the control group. Therefore, an exercise programme in combination with FES is recommended as the preferred intervention to maintain or improve bone formation, as FES has a synergistic effect on bone health in patients with osteopenia.

Abstract The present study evaluates the effects of aerobic exercise and ethanolic bitter orange peel extract on the expression of cardioprotective genes in female rats fed a high-fat diet (HFD). From the Islamic Azad University's Central Tehran Branch animal facility, 30 adult female rats of the Wistar strain were randomly assigned to five groups (six rats per group): 1) normal diet control (ND-C), 2) HFD control (HFD-C), 3) HFD aerobic exercise (HFD-AE), 4) HFD ethanolic bitter orange peel extract (HFD-BP), and 5) HFD aerobic exercise and ethanolic bitter orange peel extract (HFD-AE-BP). A normal diet was supplemented with 20% palm oil, 1.5% cholesterol, and 0.25 cholic acid to induce obesity. Before the intervention, the subjects received a HFD for four weeks, then continued it for another four weeks during the intervention. During the four-week aerobic exercise protocol, treadmill running was performed at a moderate intensity. An ethanol extract of bitter orange peel was administered orally to rats at a dose of 100 milligrams per kilogram of body weight for four weeks. After euthanasia, left ventricle myocardium was collected for real-time PCR analysis of CTRP9, LKB1, and AMPK gene expression. In the HFD-C, CTRP9 (P=0.001), LKB1 (P=0.001), and AMPK (P=0.001) genes were significantly lower than in the ND-C. Aerobic exercise significantly increased their expression compared with the HFD-C (P=0.001). Comparing HFD-C with ethanolic bitter orange peel extract, ethanolic bitter orange peel extract increased gene expression significantly (P=0.001). This indicates that the simultaneous use of these two interventions was able to add up the effects of each and did not have a synergistic effect. However, since the magnitude of change when these two interventions were combined was greater than the effect of each alone, the combination of AE and BP was greater than the effect of each alone, suggesting that these two interventions may be used to mitigate cardiac complications under HFD conditions.

Abstract Aging is associated with mitochondrial dysfunction, which leads to decreased cellular function and the development of age-related diseases. Exercise training is considered one of the most effective strategies for improving muscle cell function. The aim of the present study was to investigate the effect of six-week combined exercise on mitochondrial dynamics and biogenesis markers (MFN1, DRP1) as well as oxidative stress markers (MDA and SOD) in fast- and slow-twitch muscles of aged rats. In this study, 16 male Wistar rats (463.2 ± 9.3 g) were randomly divided into two groups (n=8 per group): control and resistance-endurance training. The training group underwent combined resistance-endurance training, 6 days a week for 6 weeks (3 resistance days, 3 endurance days). Forty-eight hours after the last training session, animals were sacrificed and fast-twitch (gastrocnemius) and slow-twitch (soleus) muscle tissues were collected. Gene expression levels of mitofusin 1 (MFN1), dynamin-related protein 1 (DRP1) were measured by real-time PCR (RT-PCR). In slow-twitch muscle, exercise training significantly increased mRNA expression levels of SOD genes, and significantly decreased mRNA expression of DRP1 and the concentration of MDA compared to the control group (p<0.05). Similarly, in fast-twitch muscle, six weeks of combined training significantly increased SOD gene expressions and decreased DRP1 mRNA and MDA levels compared to controls (p<0.05). Combined exercise training positively modulates mitochondrial biogenesis and dynamics markers (decreased DRP1 mRNA) and enhances antioxidant capacity (increased SOD gene expression and enzyme activity, decreased MDA levels) in both fast- and slow-twitch muscles of aged rats, highlighting its significant role in mitigating age-associated mitochondrial dysfunction. These findings reflect improvements in markers of mitochondrial quality control and oxidative stress rather than direct measurements of mitochondrial function.